One of the theories of aging postulates that aging is intimately related to long-term minor grade histoincompatibility reactions among the body's population of cells (1,2). We have observed that the thymus contains cells which possess receptors to self antigens (RSA), i.e., to autologous or syngeneic erythrocytes. Receptor activity can be established by both rosette formation (T-RFC) or by blast transformation of virgin thymus cells within 24-48 hours after contact with syngeneic erythrocytes. A non-strain specific small molecular weight serum factor (SF1) has been found to block both T-RFC formation and blast transformation in vitro. Based on these findings we propose that cells that can recognize self-antigens are held in check by circulating mediators produced by other cells which prevent recognition of antigens. These studies will be carried out in the short-lived, auto-immune (hemolytic anemia) prone NZB, the normal-lived Balb/c and the long-lived C57BL/6J mice. The theoretical importance of elucidating the function of the thymic histoincompatible population is exceedingly important since this may be the general mechanism to account for some of the phenomena accompanying aging, auto-immune diseases, and cancer.